Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BTX-9341 in Advanced and/or Metastatic Breast Cancer

A First-in-Human, Open-Label, Dose Escalation and Expansion Trial of BTX-9341 in Participants With Advanced and/or Metastatic Breast Cancer

The purpose of this study is to test BTX-9341 alone or in combination with fulvestrant (a currently marketed medication for breast cancer) in participants with advanced and/or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. The study includes a dose escalation part (Part A) where small groups of participants will receive increasing doses of BTX-9341 or BTX-9341 + fulvestrant followed by a dose expansion part (Part B) where participants will receive the dose of BTX-9341 selected in Part A + fulvestrant.

This first-in-human (FIH), Phase 1 study of BTX-9341 is multicenter, nonrandomized, and open-label to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of BTX-9341 in participants with advanced and/or metastatic HR+/HER2 breast cancer. The study will include a dose escalation part (Part A) followed by a dose expansion part (Part B). During Part A, BTX-9341 will initially be dose escalated alone and then in combination with fulvestrant. A single combination therapy cohort of BTX-9341 + fulvestrant will be further explored in Part B. BTX-9341 will be administered orally in 28-day treatment cycles.

Inclusion Criteria:

• Metastatic and/or locally advanced HR+/HER2- breast cancer (dose escalation: measurable disease and/or at least 1 lytic or mixed [lytic + sclerotic] bone lesion that can be assessed by CT or MRI or non-measurable disease [including bone lesions]; dose expansion: measurable disease)

• Dose escalation: (a) received not more than 1 chemotherapy in the metastatic/advanced setting; (b) no limit to the lines of endocrine therapy (monotherapy or combination therapy) in the metastatic setting; (c) received CDK4/6 inhibitor therapy

• Dose expansion: (a) received not more than 1 chemotherapy in metastatic/advanced setting; (b) received not more than 2 lines of endocrine therapy (monotherapy or combination therapy) and must have been on prior endocrine therapy for at least 6 months before progression; (c) received at most 2 lines of CDK4/6 inhibitor therapy (1 in the adjuvant setting and 1 in the metastatic setting) and must have been on prior CDK4/6 inhibitor therapy for at least 6 months

• Acceptable hematologic function

  1. ANC ≥ 1500 per mL. Note: Use of growth-factors to maintain the ANC criterion is prohibited.
  2. Platelet count ≥ 100,000 per mL. Note: Use of transfusions or thrombopoietic agents to achieve the baseline platelet count criterion is prohibited.
  3. Hemoglobin ≥ 9.0 g/dL. Note: Packed red blood cell transfusion is allowed up to 14 days prior to trial entry.

• Acceptable liver function

  1. Bilirubin ≤ 2.0 × institutional upper limit of normal (ULN) (or < 3.0 × institutional ULN if Gilbert's disease is present)
  2. Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × institutional ULN (≤ 5.0 × institutional ULN if liver metastases present)
  3. Alkaline phosphatase ≤ 2.5 × institutional ULN (≤ 5.0 × institutional ULN if bone or liver metastases present)

• Able and willing to sign informed consent

• Meets all study requirements in the opinion of the Investigator

Exclusion Criteria:

• RB1 (retinoblastoma) gene mutation
• Symptomatic visceral disease
• Clinical evidence or history of central nervous system metastasis
• Abnormalities in coagulation, such as bleeding diathesis, or treatment with anticoagulants precluding injections of fulvestrant or luteinizing hormone-releasing hormone (LHRH) agonist